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In the last years, optical fiber sensors have proven to be a reliable and versatile biosensing tool. Optical fiber biosensors (OFBs) are analytical devices that use optical fibers as transducers, with the advantages of being easily coated and biofunctionalized, allowing the monitorization of all functionalization and detection in real-time, as well as being small in size and geometrically flexible, thus allowing device miniaturization and portability for point-of-care (POC) testing. Knowing the potential of such biosensing tools, this paper reviews the reported OFBs which are, at the moment, the most cost-effective. Different fiber configurations are highlighted, namely, end-face reflected, unclad, D- and U-shaped, tips, ball resonators, tapered, light-diffusing, and specialty fibers. Packaging techniques to enhance OFBs’ application in the medical field, namely for implementing in subcutaneous, percutaneous, and endoscopic operations as well as in wearable structures, are presented and discussed. Interrogation approaches of OFBs using smartphones’ hardware are a great way to obtain cost-effective sensing approaches. In this review paper, different architectures of such interrogation methods and their respective applications are presented. Finally, the application of OFBs in monitoring three crucial fields of human life and wellbeing are reported: detection of cancer biomarkers, detection of cardiovascular biomarkers, and environmental monitoring.